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Contrasting DNA damage checkpoint responses in epithelium of the human seminal vesicle and prostate.
MedLine Citation:
PMID:  22072329     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Prostate and seminal vesicle are two similar hormone responsive human organs that differ dramatically in their cancer incidence. DNA damage response (DDR) is required for maintenance of genomic integrity. METHODS: In this study we investigated the DDR and cell cycle checkpoint activation of these organs using orthotopic cultures of human surgery-derived tissues and primary cultures of isolated prostate and seminal vesicle cells. RESULTS: We find that the activation of ATM signaling pathway by ionizing radiation (IR) was comparable in both tissues. Previously, we have shown that the prostate secretory cells express low levels of histone variant H2AX and phosphorylated H2AX (γH2AX) after IR. Here we demonstrate that H2AX levels are low also in the secretory seminal vesicle cells suggesting that this is a common phenotype of postmitotic cells. We consequently established primary epithelial cell cultures from both organs to compare their DDR. Interestingly, contrary to human prostate epithelial cells (HPEC), primary seminal vesicle epithelial cells (HSVEC) displayed effective cell cycle checkpoints after IR and expressed higher levels of Wee1A checkpoint kinase. Furthermore, HSVEC but not HPEC cells were able to activate p53 and to induce p21 cell cycle inhibitor. DISCUSSION: Our results show that during replication, the checkpoint enforcement is more proficient in the seminal vesicle than in the prostate epithelium cells. This indicates a more stringent enforcement of DDR in replicating seminal vesicle epithelial cells, and suggests that epithelial regeneration combined with sub-optimal checkpoint responses may contribute to high frequency of genetic lesions in the prostate epithelium. Prostate © 2011 Wiley Periodicals, Inc.
Authors:
Sari Jäämaa; Anna Sankila; Ville Rantanen; Karita Peltonen; Päivi M Järvinen; Taija M Af Hällström; Mirja Ruutu; Kimmo Taari; Leif C Andersson; Marikki Laiho
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-9
Journal Detail:
Title:  The Prostate     Volume:  -     ISSN:  1097-0045     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Affiliation:
Molecular Cancer Biology Program and Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Virology, University of Helsinki Hospital Laboratory Diagnostics, Helsinki, Finland.
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